Farida Mohamed Swaify

19100411
Group 4
 Assignment 1
Miss SN, a 24-year-old beauty therapist, was brought in at 11 am by ambulance from her
place of work. On admission she was severely short of breath, drowsy, and unable to speak
more than a couple of words at a time. Miss SN had been complaining of flu-like symptoms
and a worsening cough for the past few days. That morning she had started to complain of
increasing difficulty in breathing. She had been seen using her inhalers several times, and had
started to panic and then collapsed. The paramedic diagnosed an asthma attack and
administered a 2.5 mg dose of salbutamol via a nebuliser, with some improvement in
shortness of breath, and 35% oxygen via a face mask. Miss SN was able to confirm that she
had a past medical history of asthma. On examination she was tachypnoeic (respiratory rate
of 28 breaths per minute) and tachycardic (140 beats per minute (bpm)). Her blood pressure
was 150/95 mmHg with no paradoxus. On auscultation her chest was almost silent.. Chest X-
ray showed no areas of consolidation and excluded a diagnosis of pneumothorax.
After 15 minutes of 35% oxygen in the ambulance her oxygen saturation (SpO2) was 85%
and her arterial blood gases were: - PaO2 6.7 kPa (reference range 10.0–13.3)
- HCO3 22 mmol/L (22–26) - PaCO2 3.7 kPa (4.67–6.0)
- pH 7.47 (7.35–7.45)
Neurological observations were normal, as was her temperature (36.6°C).
Her white cell count was 6.5 × 109/L (4–10 × 109/L).
Miss SN was immediately given 60% oxygen via a high-flow mask and an intravenous (IV)
sodium chloride 0.9% drip was started. She was moved to an acute medical ward and the
following drugs were prescribed:
- IV hydrocortisone 200 mg immediately, then 100 mg times a day 6-hourly
- IV co-amoxiclav 1200 mg three times a day
- IV aminophylline 250 mg immediately followed by 1 g 6 L oxygen/min in 1 L sodium
chloride 0.9% to run over 24 hours
- Salbutamol 5 mg nebulised six with 6 L oxygen/min - Ipratropium 500 micrograms
nebulised four times a day
1. What important signs and symptoms of a life-threatening exacerbation of asthma
does Miss SN exhibit?
2. Outline a pharmaceutical care plan for Miss SN.
3. Write down the mechanism of action for each drug used in her therapy?
4. What are the precautions that must be taken during this therapy to avoid any
adverse effects?
5. Which parameters would you want to monitor during the acute phase of Miss SN’s
asthma attack? 6. If Miss SN was diagnosed with COPD, write down the clinical
similarities and differences between a patient with asthma and one with COPD?
Miss SN exhibits several signs and symptoms of a life-threatening exacerbation of asthma,
including:

 Severe shortness of breath

 Inability to speak more than a couple of words at a time
 Worsening cough
 Increasing difficulty in breathing
 Use of inhalers multiple times
 Panic and subsequent collapse
 Tachypnea (rapid breathing)
 Tachycardia (high heart rate)
 Silent chest on auscultation
 Unrecordable peak expiratory flow (PEF)
 Low oxygen saturation (SpO2) at 85%
 Abnormal arterial blood gas values, such as low PaO2 and low PaCO2

These signs and symptoms indicate a severe asthma exacerbation that requires
immediate medical attention.
Pharmaceutical care plan for Miss SN:
bronchodilators: Nebulized salbutamol and ipratropium are prescribed to relieve
bronchospasm and open up the airways.
corticosteroids: Intravenous hydrocortisone is given to reduce airway inflammation and
improve breathing.
Treat infection: IV co-amoxiclav, a combination of amoxicillin and clavulanic acid, is
prescribed to address any potential respiratory infection.
Provide systemic support: IV fluids with sodium chloride 0.9% are administered to
maintain hydration and support blood pressure.
Give high-flow oxygen via a mask to improve oxygen saturation levels.
Mechanism of action for each drug used in her therapy:
Salbutamol: It is a short-acting beta-agonist that acts on beta-2 adrenergic receptors in the
airway smooth muscles which activates adenyl cyclase, resulting in the conversion of ATP to
cyclic AMP (cAMP) , and by inhibiting MLCK, salbutamol prevents the phosphorylation of
myosin light chains leading to bronchodilation and relaxation of the airways.
Ipratropium: It is an anticholinergic bronchodilator that blocks the action of acetylcholine on
airway smooth muscles, resulting in bronchodilation.( passive bronchodilation)
Hydrocortisone: It is a corticosteroid that reduces airway inflammation by suppressing the
immune response and inhibiting the production of inflammatory mediators.
Co-amoxiclav: It is a combination of amoxicillin, a penicillin antibiotic, and clavulanic acid,
a beta-lactamase inhibitor. It is effective against bacterial infections commonly associated
with asthma exacerbations.
Aminophylline: It is a bronchodilator and smooth muscle relaxant that acts by inhibiting the
enzyme phosphodiesterase, leading to increased levels of cyclic adenosine monophosphate
(cAMP) and relaxation of bronchial smooth muscles.
Adenosine receptor blockade: Aminophylline competitively blocks the adenosine receptors,
particularly the A1 and A2A subtypes, present in various tissues, including the smooth
muscles of the airways.

Precautions to avoid adverse effects during therapy:

 Monitor for signs of drug hypersensitivity or allergic reactions, especially with co-
amoxiclav.
 Watch for potential drug interactions, especially between aminophylline and other
medications, as well as hydrocortisone and certain medications.
 Monitor for adverse effects of corticosteroids, such as hyperglycemia, fluid retention,
and electrolyte imbalances.
 Adjust drug dosages based on renal and hepatic function as required.
 Monitor for potential side effects of bronchodilators, such as tachycardia and tremors.
 Ensure proper infection control measures to prevent hospital-acquired infections.
 Monitor fluid balance and electrolyte levels due to IV therapy
Parameters to monitor during the acute phase of Miss SN's asthma attack:

 Oxygen saturation (SpO2)

 Respiratory rate
 Heart rate
 Blood pressure
 Peak expiratory flow (PEF)
 Arterial blood gases (PaO2, PaCO2, pH)
 Temperature
 White cell count
 Adverse drug reactions or hypersensitivity

Clinical similarities and differences between a patient with asthma and one with COPD:
Similarities:
asthma and COPD are chronic respiratory conditions that can cause shortness of breath,
coughing, wheezing, and chest tightness , they involve airway inflammation and obstruction.
Both can be exacerbated by triggers such as respiratory infections, allergens, and irritants
they often require bronchodilators and anti-inflammatory medications for management.
Differences:
Asthma typically starts in childhood or early adulthood, while COPD is more commonly seen
in older adults.
Asthma is often associated with reversible airflow limitation, while COPD is characterized by
progressive and irreversible airflow limitation.
Asthma symptoms are often intermittent and can vary in severity, while COPD symptoms are
more persistent and progressive.
Asthma exacerbations are often triggered by allergens or irritants, while COPD exacerbations
are frequently associated with respiratory infections.
Asthma is commonly associatedwith atopic conditions and a family history of allergies, while
COPD is primarily caused by smoking or exposure to environmental pollutants.
In asthma, bronchodilators are the mainstay of treatment, while in COPD, long-acting
bronchodilators and inhaled corticosteroids are often used.
Asthma may show improvement or remission with appropriate treatment, while COPD is a
progressive disease with limited reversibility.
Assignment 2
Chemotherapeutic agents , immunosuppressives and their lung toxicity
mechanisms
Bleomycin
Bleomycins are a family of compounds produced by Streptomyces verticillis. They have
potent tumour killing properties which have given them an important place in cancer
chemotherapy. They cause little marrow suppression, but pulmonary toxicity is a major
adverse effect.
The lung injury seen following bleomycin comprises an interstitial oedema with an influx of
inflammatory and immune cells. This may lead to the development of pulmonary fibrosis,
characterized by enhanced production and deposition of collagen and other matrix
components.
Bleomycin is known to generate reactive oxygen species (ROS) within the lung tissue. These
ROS can cause oxidative stress and damage to the cells of the lungs, including the epithelial
cells and the endothelial cells lining the blood vessels.

The primary target of bleomycin-induced lung injury is the alveoli, which are the tiny air sacs
in the lungs responsible for gas exchange. Bleomycin can lead to inflammation and fibrosis
(scarring) of the alveoli, impairing their function and compromising the exchange of oxygen
and carbon dioxide.
The pathophysiology of bleomycin-induced pulmonary injury involves an inflammatory
response. The drug activates immune cells, such as macrophages and neutrophils, which
release pro-inflammatory molecules and cytokines.
This inflammatory response further contributes to lung tissue damage and fibrosis.

Additionally, bleomycin can disrupt the balance between collagen production and
degradation in the lungs. It inhibits the activity of enzymes responsible for collagen
breakdown, leading to excessive collagen accumulation and fibrosis.

Overall, the mechanism of pulmonary injury caused by bleomycin involves oxidative stress,
inflammation, and fibrosis in the alveoli.
Methotrexate:
Mechanism of Toxicity: immune-mediated hypersensitivity reactions and direct cytotoxic
effects. It can cause inflammation, alveolar damage, and pulmonary fibrosis.
This immune response involves activation of T cells and the release of inflammatory
cytokines.T cells recognize methotrexate as a foreign substance and initiate an immune
response, leading to the recruitment and activation of immune cells, such as macrophages and
neutrophils.It can activate nuclear factor-kappa B (NF-κB), a transcription factor that
regulates the expression of inflammatory genes.
Activation of NF-κB leads to the production of pro-inflammatory cytokines, such as
interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6).
The release of these cytokines can promote inflammation, recruit immune cells, and
contribute to the development of lung injury.

Cyclophosphamide:
Mechanism of Toxicity: Cyclophosphamide can cause lung toxicity through its metabolite,
acrolein. Acrolein is a reactive compound that can damage lung tissues, leading to
inflammation, bronchiolitis obliterans, and interstitial pneumonitis.
Busulfan:
Busulfan can induce lung toxicity by damaging lung endothelial cells and triggering an
inflammatory response. It leads to lung injury, interstitial pneumonitis, and fibrosis.
Busulfan-induced pulmonary toxicity is characterized by the presence of acute lung
injury with associated atypical type II pneumocytes with markedly enlarged pleomorphic
nuclei and prominent nucleoli

Azathioprine:
Azathioprine can cause lung toxicity through hypersensitivity reactions and
immunosuppression. It can lead to interstitial pneumonitis and lung nodules.

Cyclosporine:

Cyclosporine-induced lung toxicity can occur as a result of endothelial cell damage,

immune-mediated reactions, and fibrosis. It can lead to interstitial pneumonitis and
bronchiolitis obliterans. Cyclosporine reduced the lung and body weight with shrinkage or
pyknotic nucleus of pneumocyte type II, degeneration of alveoli and interalveolar septum
beside microvilli on the alveolar surface, emphysema, inflammatory cellular infiltration,
pulmonary blood vessels congestion.
 The most common medicines known to cause drug-induced lupus
erythematosus are:

 Isoniazid.
 Hydralazine.
 Procainamide.
 Tumor-necrosis factor (TNF) alpha inhibitors (such as etanercept, infliximab and
adalimumab)
 Minocycline.
 Quinidine.
 Methyldopa: This medication, commonly used to treat high blood pressure during
pregnancy, has been linked to drug-induced lupus

MECHANISMS INVOLVED IN DRUG-INDUCED LUPUS

ERYTHEMATOSUS

Despite that a variety of drugs within different classes and with different
mechanisms of action have been associated with DILE, most studies
exploring pathogenic mechanisms in DILE have been primarily focused on
procainamide and hydralazine. Several mechanisms have been proposed,
including genetic predisposition, drug biotransformation and epigenetic
dysregulation in different immune cells. Mechanisms underlying the
pathogenesis of DILE are in the figure below
Genetic predisposition, drug biotransformation and epigenetic dysregulation are
three important components of current proposed pathogenic mechanisms of DILE.
Instead of working independently, these factors are likely to interact with each other
to cause DILE. Genetic predisposition: Studies revealing genetic predisposition could
be summarized in three main aspects, listed in the left upper circle.
Biotransformation: Procainamide undergoes neutrophil-mediated oxidative
metabolism to produce procainamide hydroxylamine (PAHA). PAHA,
myeloperoxidase (MPO), and reactive oxygen species contribute to direct
cytotoxicity. Epigenetic dysregulation: Drugs and some drug metabolites exert
epigenetic dysregulation on T cells and B cells (1,2), macrophages (3) and
neutrophils (4), which eventually leads to autoreactive T cell and B cell generation,
triggering DILE.
Management
Symptoms of drug-induced lupus erythematosus (DILE) usually clear within weeks of
stopping the culprit drug; however, residual antibodies may persist for extended
periods after discontinuance of the identified causative agent. Generally, no other
specific treatments are known.

If patients with DILE are given anti-inflammatory medication, this may mask the
symptoms and thus potentially result in misdiagnosis. Low doses of systemic
corticosteroids may be prescribed for short periods if the symptoms of DILE are
severe (eg, polyarthritis resulting in debilitating inflammation in many joints
simultaneously).
No specific activity restrictions are recommended. Normal activity may resume when
arthralgias and myalgias resolve.Monitor antinuclear antibody levels—anti-ssDNA,
anti-dsDNA, and antihistone antibody levels—serum complement levels, and
urinalysis findings. Continue to monitor cardiac, renal, and pulmonary function if any
of these were initially involved. Nonsteroidal anti-inflammatory drugs (NSAIDs) to
treat arthritis and pleurisy can be used .

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